Monocarbonyl curcumin analogues: heterocyclic pleiotropic kinase inhibitors that mediate anticancer properties.
Monocarbonyl curcumin analogues: heterocyclic pleiotropic kinase inhibitors that mediate anticancer properties.
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DOI：
10.1021/jm4002692
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发表时间：
2013-05-09
影响因子：
7.3
通讯作者：
Snyder, James P.
中科院分区：
文献类型：
--
作者：
Brown, Andrew;Shi, Qi;Moore, Terry W.;Yoon, Younghyoun;Prussia, Andrew;Maddox, Clinton;Liotta, Dennis C.;Shim, Hyunsuk;Snyder, James P.
姜黄素是咖喱粉的生物活性成分。一类与结构相关的模拟物具有类似的抗炎和抗癌特性。通过探索激酶抑制的趋势，研究了其作用机制。在与多种形式的癌症相关的50个蛋白的筛选中，该系列中的一个成员(4，EF31)对10种酶的≥抑制率在5μM时为85%，而22种蛋白的≥抑制率为40%。IC50的S对一组扩展的姜黄素类似物建立了效价顺序，对4的IKKATP2和AKT2酶动力学分析表明，β竞争占主导地位的混合抑制模型。我们的姜黄素模拟物通常对丝氨酸/苏氨酸激酶具有选择性。选择性和效力趋势都与蛋白质序列比较兼容，而模拟的激酶结合位点几何形状提供了与混合抑制的合理相关性。总体而言，这些类似物被证明是多效性抑制剂，沿着细胞信号通路在多个点起作用。
Curcumin is a biologically active component of curry powder. A structurally-related class of mimetics possesses similar anti-inflammatory and anticancer properties. Mechanism has been examined by exploring kinase inhibition trends. In a screen of 50 kinases relevant to many forms of cancer, one member of the series (4, EF31) showed ≥85% inhibition for ten of the enzymes at 5 μM, while twenty-two of the proteins were blocked at ≥40%. IC50’s for an expanded set of curcumin analogs established a rank order of potencies, and analyses of IKKβ and AKT2 enzyme kinetics for 4 revealed a mixed inhibition model, ATP competition dominating. Our curcumin mimetics are generally selective for Ser/Thr kinases. Both selectivity and potency trends are compatible with protein sequence comparisons, while modeled kinase binding site geometries deliver a reasonable correlation with mixed inhibition. Overall, these analogs are shown to be pleiotropic inhibitors that operate at multiple points along cell signaling pathways.
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影响因子：
2.3
作者：
Adams, BK;Cai, JY;Shoji, M
通讯作者：
Shoji, M
影响因子：
3.5
作者：
Adams, BK;Ferstl, EM;Shoji, M
通讯作者：
Shoji, M
影响因子：
5.1
作者：
Awasthi, S;Pandya, U;Ansari, GAS
通讯作者：
Ansari, GAS
影响因子：
3.6
作者：
Kasinski, Andrea L.;Du, Yuhong;Fu, Haian
通讯作者：
Fu, Haian
DOI：
10.4161/cc.8.2.7551
发表时间：
2009-01-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Chen Y;Craigen WJ;Riley DJ
通讯作者：
Riley DJ